Treatment of depression with transcranial magnetic stimulation using an H-coil (dTMS)

A systematic review and assessment of medical, economic, social and ethical aspects. An HTA Report

This report is part of a government assignment regarding mental illnesses and consists of a systematic review of therapeutic effects and adverse events in the treatment of depression with deep transcranial magnetic stimulation (dTMS), which is a variant of repetitive transcranial magnetic stimulation (rTMS).

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SBU Assessment

Presents a comprehensive, systematic assessment of available scientific evidence for effects on health, social welfare or disability. Full assessments include economic, social and ethical impact analyses. Assessment teams include professional practitioners and academics. Before publication the report is reviewed by external experts, and scientific conclusions approved by the SBU Board of Directors.

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Published: Report no: 318 Registration no: SBU 2020/427 ISBN: 978-91-88437-60-0 https://www.sbu.se/318e

Conclusions

  • It is uncertain how the effects of dTMS compare with those of rTMS with a figure-of-8 coil. There are no reliable studies comparing dTMS with other treatments for depression.
  • Four weeks of treatment with dTMS compared with treatment with a sham coil results in an 11% increase in remission (between 1% and 22%) in patients with depression who were previously treated with antidepressants (⊕⊕◯◯). The long-term effects of dTMS treatment are uncertain.
  • Epileptic seizures can occur during dTMS treatment, but they are uncommon. There are no indications of cognitive side effects. Reports of local pain increases with 22% (between 15% and 28%) in patients treated with dTMS compared to patients treated with a sham coil (⊕⊕⊕◯).

The intention behind the development of dTMS was to achieve a larger effect than that observed with the established treatment using rTMS with a figure-of-8-coil in patients previously treated with antidepressants. The effects of dTMS in comparison with other treatments have not been sufficiently evaluated; however, the effect size seems to be similar to that achievable with rTMS using a different coil type.

The studies evaluating dTMS have included different populations and different numbers of previous treatment attempts. The possibility that dTMS is more effective for specific groups of patients cannot be excluded, and it would be valuable to perform studies focusing on well-defined patient groups that currently lack suitable alternative treatments.

Background

Alternative treatments are needed for patients with depression who do not improve after treatment with antidepressant drugs or psychological treatment. One alternative is rTMS, where an electromagnetic coil is placed on the patient’s head and repetitive pulses create a changing magnetic field that induces electric current that stimulates parts of the brain that are thought to be involved in the mechanisms of depression. dTMS is a variant of rTMS, in which a different shaped coil is used. The coil used in dTMS is referred to as an H-coil, whereas the most common coil type in rTMS is a figure-of-8 coil.

Aim

To assess the effects and adverse events of treating depression with dTMS. The questions asked were as follows:

  • Does dTMS affect depression when the depressive state is assessed at the end of treatment or during follow-up sometime after the end of treatment?
  • If dTMS has a statistically significant therapeutic effect, can maintenance treatment maintain this effect?
  • What side effects and complications are there with dTMS treatment, and how common are they?

Method

This systematic review was conducted in accordance with the PRISMA statement. The protocol is registered in Prospero (CRD42020193623, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193623). The certainty of evidence was assessed using GRADE (https://gdt.gradepro.org/app/handbook/handbook.html).

Inclusion criteria

Population: Patients with unipolar or bipolar depression according to DSM-III to DSM-5 or ICD-10 criteria.

Intervention: Transcranial magnetic stimulation with an H-coil.

Control: Sham coil, other treatments such as rTMS using a different coil type, ECT, or antidepressant drugs, or treatment with another dose of dTMS.

Outcome: Percentage of patients in remission, percentage of patients with a response or change in score on a depression-rating scale. Adverse events and complications of treatment.

Study design: Randomised controlled trials.

Search period: From 2014 to 2020. Final search on February 24, 2020.

Databases searched: Cochrane Library (Wiley), EMBASE (Embase.com), PsycINFO (EBSCO), PubMed (NLM).

A complementary search of Clinicaltrials.gov was performed in September 2020 for studies using dTMS for the treatment of depression.

Client/patient involvement: No.

Results

Five randomised clinical trials that described the effects and side effects of dTMS were included in this systematic review (Figure 1). These studies included 582 participants. The results of the assessment are summarised in Figure 1 and Table 1 below.

Flow chart of the article selection procedure. Started with screening of 2089 records and in the end were 5 studies included in the analysis

Figure 1 Flow chart of the article selection procedure.

Table 1 Summary of findings
CI = Confidence interval; MD = Mean difference; NA = Not applicable; RD = Risk difference; RR = Risk ratio; SD = Standard deviation.

1 Deducion of 1 point for risk of bias due to uncertainties in the reporting, especially regarding the largest study, and because three of four studies were sponsored by the company that developed the product, and it is unclear how involved the company was in these studies.
2 Deduction of 1 point for precision as there were few participants and few events in the studies.
3 Deduction of 1 point for precision as there were few participants and studies.
4 Deduction of 3 points for precision as there was only one study, which had few participants.
* Mean difference and standard deviation cannot be reported as the change in depression score was reported in different ways across the studies.
OutcomeNumber of participants
(Number of studies)
Reference
Study design		Result
MD (SD)		Effect
RR/RD or MD
(95% CI)		Certainty of evidenceDeduction
dTMS compared with a sham coil at end of treatment
Increase in the proportion achieving remission 354
(4)
[1-4]
RCT		 dTMS: 0.26 (0.12)
sham coil: 0.15 (0.01)		 RD: 0.11 (0.01 to 0.22)
(RR: 1.88 (1.22 to 2.88))		 Low
⊕⊕◯◯		 –1 risk of bias1
–1 precision2
Increase in the proportion achieving a response 354
(4)
[1-4]
RCT		 dTMS: 0.34 (0.17)
sham coil: 0.20 (0.03)		 RD: 0.13 (0.01 to 0.25)
(RR: 1.72 (1.2 to 2.46))		 Low
⊕⊕◯◯		 –1 risk of bias1
–1 precision2
Decrease in depression score 354
(4)
[1-4]
RCT		 NA* MD: –2.85
(–4.18 to −1.51)		 Low
⊕⊕◯◯		 –1 risk of bias1
–1 precision3
dTMS compared with rTMS with a figure-of-8 coil
Increase in the proportion achieving remission 147
(1)
[5]
RCT		 dTMS: 0.60
rTMS: 0.43		 RD: 0.17 (0.01 to 0.33)
(RR: 1.40 (1.01 to 1.93))		 Very low
⊕◯◯◯		 –3 precision4
Increase in the proportion achieving a response 147
(1)
[5]
RCT		 dTMS: 0.67
rTMS: 0.44		 RD: 0.23 (0.07 to 0.38)
(RR: 1.52 (1.12 to 2.05))		 Very low
⊕◯◯◯		 –3 precision4
Decrease in depression score 147
(1)
[5]
RCT		 dTMS: −10<
rTMS: −7		 MD: –3.00
(−5.03 to −0.97)		 Very low
⊕◯◯◯		 –3 precision4
dTMS compared with a sham coil 4 weeks after end of treatment
Proportion in remission 50
(1)
[4]
RCT		 dTMS: 0.24
sham coil: 0.24		 RD: 0.00
(–0.24 to 0.24)
(RR: 1.00 (0.37 to 2.68))		 Very low
⊕◯◯◯		 –3 precision4
Increase in the proportion achieving a response 50
(1)
[4]
RCT		 dTMS: 0.32
sham coil: 0.24		 RD: 0.08
(–0.17 to 0.33)
(RR: 1.33 (0.54 to 3.29))		 Very low
⊕◯◯◯		 –3 precision4
Decrease in depression score 50
(1)
[4]
RCT		 dTMS: −9.32
sham coil: −6.08		 MD: –2.76
(–8.24 to 2.72)		 Very low
⊕◯◯◯		 –3 precision4
Adverse events of dTMS compared with a sham coil
Increase in the proportion with experience of local pain at the application site 335
(3)
[1,4,6]
RCT		 dTMS: 0.20 (0.04)
sham coil: 0.00 (0.00)		 RD: 0.22 (0.15 to 0.28)
(RR: 17.70 (4.30 to 72.81))		 Moderate
⊕⊕⊕◯		 –1 precision3

The full report in Swedish

The full report "Behandling av depression med transkraniell magnetstimulering med H-spole (dTMS)" (in Swedish)

References

  1. Kaster TS, Daskalakis ZJ, Noda Y, Knyahnytska Y, Downar J, Rajji TK, et al. Efficacy, tolerability, and cognitive effects of deep transcranial magnetic stimulation for late-life depression: a prospective randomized controlled trial. Neuropsychopharmacology 2018;43:2231-8.
  2. Levkovitz Y, Isserles M, Padberg F, Lisanby SH, Bystritsky A, Xia G, et al. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry 2015;14:64-73.
  3. Matsuda Y, Kito S, Igarashi Y, Shigeta M. Efficacy and Safety of Deep Transcranial Magnetic Stimulation in Office Workers with Treatment-Resistant Depression: A Randomized, Double-Blind, Sham-Controlled Trial. Neuropsychobiology 2020;79:208-13.
  4. Tavares DF, Myczkowski ML, Alberto RL, Valiengo L, Rios RM, Gordon P, et al. Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial. Neuropsychopharmacology 2017;42:2593-601.
  5. Filipčić I, Šimunović Filipčić I, Milovac Ž, Sučić S, Gajšak T, Ivezić E, et al. Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial. J Psychiatr Res 2019;114:113-9.
  6. U.S. Food and Drug Administration (FDA). 510(K) SUMMARY Brainsway Deep TMS System; 2013. [cited 2020 Sep 10]. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf12/k122288.pdf

Project group

Experts

  • Axel Nordenskjöld, Psychiatrist, Örebro University Hospital, Örebro
  • Björn Mårtensson, Psychiatrist, Karolinska institutet, Stockholm

From SBU

  • Susanne Johansson, Project Manager
  • Agneta Pettersson, Assistant Project Manager
  • Sara Fundell, Project Administrator
  • Klas Moberg, Information Specialist

External reviewers

  • Robert Bodén, Psychiatrist, Uppsala University Hospital, Uppsala

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